Perturbation of CD4+ and CD8+ T-cell repertoires during progression to AIDS and regulation of the CD4+ repertoire during antiviral therapy.
The T-cell antigen receptor (TCR) repertoire was studied longitudinally by analyzing the varying lengths of the beta chain CDR3 hypervariable region during the course of HIV-1 infection and following combination antiretroviral therapy. Drastic restrictions in CD8+ T-cell repertoire usage were found at all stages of natural progression and persisted during the first six months of treatment. In contrast, significant CD4+ T-cell repertoire perturbations were not found in early stages of infection but correlated with progression to AIDS. Out of ten patients presenting with pretreatment perturbations, normalization of the CD4+ repertoire was observed in eight good responders, but not in two cases of unsuccessful therapy. These results indicate that, besides CD4+ cell count rise, an efficient control of HIV replication may allow qualitative modifications of the CD4+ repertoire balance.
Gorochov
G
G
Laboratoire d'Immunologie Cellulaire, CERVI, URA CNRS 625, Hôpital Pitié-Salpétrière, Paris, France. guy.gorochov@psl.ap-hop-paris.fr
Neumann
A U
AU
Kereveur
A
A
Parizot
C
C
Li
T
T
Katlama
C
C
Karmochkine
M
M
Raguin
G
G
Autran
B
B
Debré
P
P
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000276:immunology*
D019380:Anti-HIV Agents; D011948:Receptors, Antigen, T-Cell